Concomitant Granulocyte Colony-Stimulating Factor and Induction Chemoradiotherapy in Adult Acute Lymphoblastic Leukemia: A Randomized Phase III Trial

• Published in: Blood Vol. 86; no. 2; pp. 444 - 450
• Main Authors: Ottmann, Oliver G., Hoelzer, Dieter, Gracien, Edith, Ganser, Arnold, Kelly, Krys, Reutzel, Regina, Lipp, Thomas, Busch, Friedrich W., Schwonzen, Martin, Heil, Gerhard, Wandt, Hannes, Koch, Peter, Kolbe, Karin, Heyll, Axel, Bentz, Martin, Peters, Stefan, Diedrich, Helmut, Dethling, Jürgen, Meyer, Peter, Nowrousian, Mohamed R., Löffler, Barbara, Weiss, Adelheid, Kneba, Michael, Föller, Almut, Graf, Martina, Hecht, Thomas
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-07-1995; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide - administration & dosage; Cytarabine - administration & dosage; Disease-Free Survival; Female; Filgrastim; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematologic and hematopoietic diseases; Humans; Immunologic Factors - therapeutic use; Infection Control; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Mercaptopurine - administration & dosage; Methotrexate - administration & dosage; Middle Aged; Neutropenia - prevention & control; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prospective Studies; Recombinant Proteins - therapeutic use; Remission Induction; Survival Analysis; Treatment Outcome; Antineoplastic agent; Human; Acute; Cytokine; Malignant hemopathy; Radiotherapy; Chemotherapy; Granulocyte colony stimulating factor; Polypeptide; Lymphoproliferative syndrome; Immunotherapy; Phase II trial; Adult; Acute lymphocytic leukemia
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.2.444.bloodjournal862444

This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patients were randomly assigned to receive either G-CSF (n = 37) or no growth factor (n = 39) in conjunction with a uniform chemotherapy consisting of cyclophosphamide, cytarabine, mercaptopurine, intrathecal methotrexate, and cranial irradiation. The median duration of neutropenia (absolute neutrophil count < 1 × 109/L) during chemotherapy was 8 days in patients receiving G-CSF, compared with 12.5 days in the control group [P < .002). A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation (P = .13). Infections occurred in 43% and 56% of patients in the G-CSF and control arm, respectively (P = .25); the incidence of nonviral infections was reduced by 50%, from 32 episodes in the control arm to 16 episodes in the G-CSF arm. Prolonged interruptions of chemotherapy administration were less frequent, with delays of 2 weeks or more occurring in only 24% of patients receiving G-CSF as opposed to 46% in the control arm (P = .01). Accordingly, chemotherapy was completed significantly earlier with the use of G-CSF (39 v 44 days, P = .008). With a median follow-up of 20 months, the probability of disease-free survival was 0.45 in the G-CSF group and 0.43 in the control group [P = .34). In conclusion, adult ALL patients appear to benefit by the simultaneous administration of G-CSF with induction chemotherapy because of a significant reduction in the duration of neutropenia, a trend to fewer infections, and a more rapid completion of chemotherapy.